The objective of this proposal is to determine the functional role of PLAC1, a novel trophoblast-specific and X-linked gene, in placental and fetal development. A significant role for PLAC1 in placental development is strongly suggested by its tissue-specific and temporal patterns of expression. This is strengthened by a fetal growth retardation phenotype and placental growth abnormalities associated with X chromosome deletions in the region to which PLAC1 maps. Because of a paucity of genes in this region of the X-chromosome, PLAC1 is the leading candidate gene responsible for the observed phenotype. PLAC1 shares sequence homology with the zona pellucida protein 3 (ZP3) suggesting it may be involved in specific cellular interactions at the maternal-fetal interface, possibly acting as a cell surface receptor. Viewed collectively, these observations suggest that PLAC1 encodes a placenta-specific protein of importance to mammalian reproduction. Preliminary evidence suggests that PLAC1 expression is markedly upregulated during trophoblast differentiation and limited to the differentiated syncytiotrophoblast and trophoblasts of the chorion laeve. The proposed studies will help define the role of PLAC1/Plac1 in placental growth by pursuing the following aims: First, the PLAC1 polypeptide will be characterized, biochemically, and its subcellular localization in the normal trophoblast defined. Specific protein-protein interactions important to its function will be identified. Second, the role of Plac in placental and embryonic growth will be studied at the whole animal level in a mouse mutant model. Given the restricted nature of PLAC1/Plac1 expression, these studies will likely provide novel insights into mechanisms important in placental and fetal development. [unreadable] [unreadable] [unreadable]